Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles

Abstract

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

Biodistribution and toxicity of epitope‐functionalized dextran iron oxide nanoparticles in a pregnant murine model

“…This finding is important because similar formulations can be employed for targeted delivery and treatment of other disease entities in these organs. These observations are in agreement with other reported results demonstrating significant accumulation in the lungs and liver for intravenously injected NPs (Park et al, ; Sharma et al, ). For example, Sharma et al injected citrate‐stabilized IONP surface‐coated with negatively charged carboxymethyl dextran (CM) or positively charged PEG‐Polyethyleneimine (PEI) at a dose of 8 mg NPs/kg into retro‐orbital plexus of male athymic nude mice.…”

“…This finding is important because similar formulations can be employed for targeted delivery and treatment of other disease entities in these organs. These observations are in agreement with other reported results demonstrating significant accumulation in the lungs and liver for intravenously injected NPs (Park et al, 2016;Sharma et al, 2018). CA-IONPs were deposited mainly in the lungs (Sharma et al, 2018).…”

“…For example, Sharma et al injected citrate‐stabilized IONP surface‐coated with negatively charged carboxymethyl dextran (CM) or positively charged PEG‐Polyethyleneimine (PEI) at a dose of 8 mg NPs/kg into retro‐orbital plexus of male athymic nude mice. The CM‐modified CA‐IONPs demonstrated highest deposition in spleen and liver, while PEG‐PEI CA‐IONPs were deposited mainly in the lungs (Sharma et al, ). Further, PEG‐PEI CA‐IONPs appeared to be localized within lung epithelial cells, whilst CM‐coated CA‐IONPs were localized in the interstitial spaces, ostensibly due to surface charge differences.…”

“…Investigating the clearance rate of IONPs, we reported serum total iron concentration similar to saline‐treated controls at 24 h postinjection, suggesting clearance of SNAREs. Several other groups have also demonstrated serum iron concentration as an effective measurement of IONPs in the blood and blood clearance at 24 hr (Feng et al, ; Sharma et al, ). To Elucidate the effect of PEG on NP clearance, we compared the clearance rates by determining the AUC for DIONP‐ and SNARE‐treated dams.…”

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

“…e coating layer minimized the interactions between the iron core and plasma proteins and enhanced the circulation time. Iron deposition from NPs possessing a negative surface potential was observed to have higher accumulation in the liver and spleen [65].…”